Oncolytic virotherapy for hepatocellular carcinoma: A potent immunotherapeutic landscape

Table 1 Clinical trials of oncolytic virus for hepatocellular carcinoma

Trial number	Virus	Disease	Status	Interventions	Trail phase	Study start
NCT00844623	TK99UN	HCC	Completed	Alone	I	2002
NCT00003147	Ad5CMV-p53 gene	Liver cancer	Completed	Alone	I	1998
NCT02509169	rAd-p53	HCC	Unknown status	Alone	II	2014
NCT00300521	ADV-TK	Advanced HCC	Completed	Alone	II	2000
NCT02418988	rAd-p53	Advanced HCC	Unknown status	TACE	II	2014
NCT01869088	H101	HCC	Unknown status	TACE	III	2013
NCT03790059	H101	HCC	Unknown status	RFA	Not applicable	2016
NCT03313596	ADV-Tk	Advanced HCC	Unknown status	LT	III	2013
NCT05113290	H101	HCC	Unknown status	Sorafenib	IV	2021
NCT00629759	JX-594	Primary hepatocellular carcinoma	Completed	Alone	I	2006
NCT00554372	JX-594	Primary hepatocellular carcinoma	Completed	Alone	II	2008
NCT02562755	JX-594	HCC	Completed	Sorafenib	III	2015
NCT01387555	JX-594	HCC failed sorafenib treatment	Completed	Alone	II	2008
NCT02509507	T-Vec	HCC et al	Active, not recruiting	Pembrolizumab	I/II	2016
NCT04313868	GEN2	Metastatic HCC	Recruiting	Alone	I	2014
NCT05223816	VG161	HCC et al	Recruiting	Nivolumab	II	2023
NCT01628640	VSV (IFN-β)	HCC	Active, not recruiting	Alone	I	2012
NCT04665362	M1 virus	Advanced/metastatic hepatocellular carcinoma	Unknown status	Anti PD-1 antibody and apatinib	I	2021

VSV: Vesicular stomatitis virus; IFN-β: Interferon-beta; HCC: Hepatocellular carcinoma.

Table 2 Representative oncolytic virus for hepatocellular carcinoma

Virus name	Mode of actions/target	Virus Modification	Potential implications	Ref.
ZD55-IL-24	Combine cisplatin in vitro/Bel-7404, SMMC-7721	IL-24 gene, E1B 55 kDa deletion	Enhance selective cytotoxicity	[11]
ZD55-TRAIL-IETD-Smac	Intratumoral injection/Bel-7404 nude mice model	TRAIL and Smac gene, E1B 55 kDa deletion	Enhance synergistic anti-tumor effect	[12]
Ad.wnt-E1A (Δ24bp)-TSLC1	Intratumoral injection/MHCC-97H nude mice model	TSLC1 gene, 24 bp deletion of E1A CR2	Enhance tumor selectivity antitumor activity	[14]
OncoVV-AVL	In vitro/Hep-3B, PLC/PRF/5, Huh7	Aphrocallistes vastus lectin	Enhance the ability of replication	[22]
T-01	Left lobe of the liver injection/HuH-7, KYN-2, PLC/PRF/5, HepG2 athymic mice model	-	Enhance oncolytic safety	[25]
VSV-β-gal	Administered via the hepatic artery/McA-RH7777 ‘‘multifocal’’ HCC in the rat liver	β-galactosidase	Enhance tumor-selective viral replication, and extensive oncolysis	[33]
Wild type REO	Oral gavage/Huh7 SCID mice model	-	Inhibit the replication of HCV in HCV-HCC	[37]
delNS1	Inoculation in vivo/STAT12/2 mice, STAT11/1 mice, C57BL/6 mice	Partial deletion of NS	Inhibit the host antiviral response	[40]
delNS1-GM-CSF	Intratumoral injection/HepG2 nude mice model	Partial deletion of NS, GM-CSF inserted	Enhance oncolytic efficacy and safety	[42]
rNDV/F3aa (L289A)	Administered via the hepatic artery/McA-RH7777 ‘‘multifocal’’ HCC in the rat liver	A single amino acid substitution from alanine to L289A in the F protein	Enhance tumor specific syncytial formation and necrosis	[46]
VG9-IL-24	Intratumoral injection/SMMC-7721 nude mice model	IL-24	Induce apoptosis of tumor cells	[51]
Ad-GD55-α-TIM-3	Intratumoral injection/PBMC mixed Bel-7404 BALB/c nude mice model	GP73 promoter and α-TIM-3	Enhance the antitumor efficacy and the local immune response	[52]
OVH-aMPD-1	Combination with TIGIT blockade In vivo/hepa1-6 nude mice model	Express a scFv against PD-1 (aMPD-1 scFv)	Remodel immunosuppressive tumor microenvironment	[59]

NDV: Newcastle disease virus; scFv: Single-chain variable fragment; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; MHC: Major histocompatibility complex; TSLC1: Tumor suppressor lung cancer 1; VSV: Vesicular stomatitis virus; REO: Reovirus; delNS1: Nonstructural protein1; TIGIT: T cell immune receptor with Ig and ITIM domains; PBMC: Peripheral blood mononuclear cell; NS: Nonstructural protein; GM-CSF: Granulocyte-macrophage colony stimulating factor; oncoVV-AVL: Aphrocallistes vastus lectin; L289A: Leucine at amino acid 289.